There are a number of prior art methods and apparatuses which are used in the detection and treatment of cancer. Fluorescent markers have been used to help identify cancerous tissue within a patient. Radio tracers or markers have also been used in the detection and treatment of cancer.
U.S. Pat. No. 5,391,547 discloses a method of using porphyrins to detect lung cancer, and more particularly, to the use of tetra-aryl porphyrins. The porphyrins are used as a fluorescent tracer for cancers of the lung. The porphyrins may be complexed with Copper 64 (64Cu) or Copper 67 (67Cu). Thus, the complex can be used as radio tracers as well. The 67Cu provides a source of beta radiation for selective destruction of lung malignancies as well as gamma radiation useful for image analysis, as by single photon emission computer tomography. The 64Cu may be used for radio tracing wherein a positron emission tomography technique can be used to locate the malignant tissue.
U.S. Pat. No. 5,087,636 to Jamieson, et al. discloses a method to identify and destroy malignant cells in mononuclear cell populations. This method includes the steps of contacting a composition of bone marrow cells or other cells with a green porphyrin of a specific compound, irradiating the cell composition with light at a wave length effective to excite fluorescence of the green porphyrin, and then detecting the presence or absence of fluorescence indicating malignancy. This reference also discloses the steps by which the bone marrow cells are removed, separated, washed and diluted to an appropriate concentration for treatment, incubated, centrifuged, and exposed to the irradiating light.
U.S. Pat. Nos. 5,308,608 and 5,149,708 to Dolphin, et al. disclose specific types of porphyrin compounds which may be used for detection, photosensitization, or the destruction of a targeted biological material when the targeted tissue is contacted with the specified porphyrin, and irradiated with light that excites the compound.
U.S. Pat. No. 5,211,938 to Kennedy, et al. discloses a method of detection of malignant and non-malignant lesions by photo chemotherapy of protoporphyrin IX precursors. 5-amino levulinic acid (5-ALA) is administered to the patient in an amount sufficient to induce synthesis of protoporphyrin IX in the lesions, followed by exposure of the treated lesion to a photo activating light in the range of 350–640 nanometers. Naturally-occurring protoporphyrin IX is activatable by light which is in the incident red light range (600–700 nanometers) which more easily passes through human tissue as compared to light of other wave lengths which must be used with other types of porphyrins. In short, the use of 5-ALA makes cell fluorescence easier to observe, and also greatly reduces the danger of accidental phototoxic skin reactions in the days following treatment since protoporphyrin IX precursors have a much shorter half life in normal tissues than other popularly used porphyrins.
Present methods relating to cancer screening using fluorescence detection systems require the use of interventional devices such as endoscopes which have the special capability of delivering specified light frequencies to a targeted tissue of a patient. These endoscopes illuminate the targeted part of the body in which cancer is suspected. The light delivered at a specified frequency illuminates an area which has previously been subjected to some type of fluorescent marker, such as a porphyrin which causes malignant cells to illuminate or fluoresce under observation of light at the specified frequency. In all cases, introduction of an endoscope into the body requires some type of sedation or general or local anesthesia. Once a tumor has been located by use of the interventional device, depending upon the type of tumor, photo chemotherapy or other treatment means can be used. However, prior to actual treatment, there must be a confirmed test of cancer. Accordingly, the tumor still needs to be sampled by an appropriate biopsy method. Generally, biopsy methods also require some type of sedation or anesthesia. Thus, traditional methods of confirming a malignancy may require at least two interventional surgical procedures.
In all uses of photodynamic therapy, it is well known that there are limitations in such therapy because of the poor penetration of the visible light required to activate the administered porophyrin so as to render it toxic to the targeted tissue. Particularly for tumors which are found deep within the body of a patient, repeated interventional procedures to treat the neoplastic tissue become infeasible. Accordingly, many types of diseased tissue cannot be effectively treated through photodynamic therapy.
Stereotaxic radio surgery is a well known procedure to treat tumorous tissue. This type of radio surgery is particularly well known for treating brain tumors. Advances in technology for delivering a collimated surgical ionizing beam now allows medical personnel to treat patients with cancerous tissue throughout the body.
One company that provides a stereotaxic radio surgery system is Accuray of Boulder, Colo. One system developed by Accuray includes the Cyberknife™ system that incorporates a linear accelerator mounted on a robotic arm thereby providing a surgeon with great flexibility in delivering a collimated beam to a targeted area. The Cyberknife has been used to radiosurgically treat many tumors and other malformations at body sites which are unreachable by other stereotaxic systems.
Accuray is the owner of two U.S. patents which claim devices and methods of carrying out stereotaxic radio surgery and radio therapy. U.S. Pat. No. 5,207,223 discloses a method and apparatus for selectively irradiating a target within a patient. A 3-dimensional mapping is provided of a region surrounding the target. A beaming apparatus emits a collimated beam. Diagnostic beams at a known non-zero angle to one another pass through the mapping region. Images of projections are produced within the mapping region. Electronic representations of the images are compared with reference data from the 3-dimensional mapping thereby locating the target. The relative positions of the beaming apparatus and the living organism are adjusted in such a manner that the collimated beam is focused on the target region despite any movement by the patient during treatment. A comparison is repeated at small time intervals and, when the comparison so indicates, adjustment is repeated, as needed, and in such a manner that the collimated beam remains focused on the target region.
U.S. Pat. No. 5,427,097 owned by Accuray discloses another apparatus and method of performing stereotaxic surgery. A robotic arm and beam generating arrangement are provided along a predetermined, non-circular and non-linear path transverse to a collimated beam path, while at the same time, the collimated beam path is directed into the target region. Thus, the radiosurgical/radiotheraputic beam can be directed through the target region from particular treatment points along the transverse path so as to define a non-spherical target region, thereby allowing treatment of irregularly shaped tumors or malformations.
One important objective of the inventions disclosed in these references owned by Accuray is to improve the ability to deliver a radiological beam which can be precisely targeted for irradiating targeted tissue, yet limiting exposure of healthy tissue. With the inventions disclosed in the two references, it is possible to perform multiple fraction radiological treatment thereby improving the ability to target and localize cancerous or malformed tissue.
While the two references discussed immediately above represent advances in stereotaxic radiosurgery and radiotherapy, these systems can be further enhanced by improving the ability to not only map targeted tissue, but also to image the tissue during the radio surgery/radio therapy procedure thereby ensuring that the radiological beam is precisely aligned with the targeted tissue. In the above references, 3-dimensional mapping is obtained by a CAT scan (CT) or by magnetic resonance imaging (MRI). As is well known, computerized tomography operates through measurement of the differential absorption of x-ray beams, and the resulting images are in the form of data which is mathematically manipulated through Fourier transform. MRI utilizes nuclear magnetic resonance properties of tissue to obtain 3-dimensional mapping. CT scanners and MRI scanners are available commercially, and the data obtained by the scanning can be placed in a digitized format whereby it can be stored and manipulated through software in a computer. Although an MRI or CT scan may be adequate under many circumstances, the disadvantages of CT scanning or MRI scanning is that these types of scans image the physical structure of tissue, and do not provide information regarding the body's chemistry, or cell function.
More recent imaging technologies include positron emission tomography (PET). A PET scan differs from the CT or MRI scan in that the PET scan analyzes cell function, which in many instances provides a better method by which to determine whether tissue is cancerous. PET typically involves the administration of a radioactive form of glucose, and then the PET scanner tracks and records signals which are emitted by the administered compound. Actively growing cancer cells typically have much higher metabolic rates than normal cells; therefore, the radioactive glucose is metabolized more quickly by these cancerous tissues, thereby creating distinct signals which can be recorded by the PET scanner. A computer then reconstructs the recorded signals into 3-dimensional digital images that show areas throughout the body where diseases are present. In addition to PET, a related imaging technology includes single photon emission computer tomography (SPECT) which is also a computerized imaging technique that produces 3-dimensional images of tissue function. As with PET scanning, a small amount of a radioactive isotope is administered to a patient, and any increased metabolic activity present at various body locations can be identified and reviewed to determine whether a patient has diseased or cancerous tissue.
One class of chemicals useful for the treatment of tumors is the porphyrins and particularly hematoporphyrin derivatives. These chemicals have been studied as a result of their selective localization and uptake into tumors and malignant tissue and their sensitization of tumor tissues to photoirradiation. It has also been suggested that these chemicals could function as delivery vehicles to target other anticancer compounds to tumor tissues due to their selective uptake into tumor tissues. For example, porphyrin molecules may chelate one of many different metal atoms which are then localized to tumor tissues. These metal atoms can be radioactive isotopes which then irradiate the surrounding tumor tissue after localization to the tumor within a metalloporphyrin. Additionally, the radioactivity emitted can be used in PET or SPECT scanning to create an image of the tumor tissue. However, even without a radioactive component, the metalloporphyrins are still effective in selectively delivering a metal atom to tumor tissues. The metal can then act as a contrast agent to enhance magnetic resonance imaging or nuclear magnetic resonance imaging. Because the localization of the metalloporphyrins is based on the chemical properties of the porphyrins themselves and their interaction with characteristics of tumor cells including large interstitial space, high capillary permeability and lack of lymphatic drainage, and not on differences in metabolic activities in tissues, they are more selectively taken up and retained by malignant cells than are radioactive glucose molecules. For this reason, the metalloporphyrins are also better contrast agents for use with the different tumor imaging techniques than are radioactive glucose molecules.
One reference that discloses the use of metalloporphyrins as imageable tumor targeting agents for radiation therapy is U.S. Pat. No. 6,566,517. This reference specifically discloses halogenated derivatives of boronated porphyrins containing multiple carborane cages which selectively accumulate in neoplastic tissue, and thus can be used in cancer therapies including boron neutron capture therapy and photodynamic therapy. Although this reference generally discusses the uses of metalloporphyrins for radiation therapy, there is no disclosure of particular procedures by which targeted tissue can be mapped, nor is there disclosure of other methods by which cancer screening or treatment therapy can be conducted other than by boron neutron capture or photodynamic therapy.